Cognitive Training and Brain Stimulation in Prodromal Alzheimer's Disease (AD-Stim)

Effects of Cognitive Training and Brain Stimulation in Prodromal Alzheimer's Disease - Randomised, Sham Controlled, Interventional Study

The aim of this study is to investigate whether a tDCS-accompanied intensive cognitive training of working memory leads to performance improvement in individuals with prodromal Alzheimer's disease.

The goal of the present study is to assess behavioral (primary) effects of a multi-session cognitive training combined with transcranial direct current stimulation (tDCS). Many studies to date have found tDCS to be an efficient method to enhance various cognitive functions by modulating cortical excitability in young adults, but its behavioral impact and underlying mechanisms in pathological aging still need to be elucidated. Individuals with prodromal Alzheimer's disease, will participate in a three-week cognitive training with concurrent online tDCS application. Cognitive performance (primary) will be examined before, during and after the intervention, in order to draw conclusions about the effect of tDCS. In addition to cognitive training, a control group, receiving sham stimulation during training, will be assessed. Follow-up sessions to assess long-term effects are planned four weeks and seven months after the post assessment. Furthermore, to assess potential predictors of tDCS effects, functional and structural parameters will be measured with MRI. The results of the study will offer valuable insights into efficacy of combined tDCS and cognitive training, as compared to training alone, in individuals with prodromal stages of Alzheimer's disease. Moreover, improved understanding of tDCS effects on cognitive training performance and underlying neural correlates may help to develop novel approaches for modulating cognitive decline in healthy and pathological aging.

Anodal transcranial direct current stimulation (tDCS), 9 sessions with 20 minutes stimulation each (current intensity of 1mA)

Intensive cognitive training of a letter memory updating task and a 3-stage Markov decision making task, 9 sessions

Performance in a memory training task (Letter updating) under anodal tDCS compared to sham condition; operationalized by working Memory Updating performance assessed with number of correctly recalled letter lists in the letter updating task, analyzed immediately after training period (anodal condition versus sham)

Performance in second memory training task (Markov decision making) under anodal tDCS compared to sham condition, analyzed immediately after training period (anodal condition versus sham)

Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

Long-term outcomes: AVLT (auditory verbal learning test) (sum of correctly recalled items trials 1-5)

Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

- structural neural correlates; assessed by grey matter volumes, cortical thickness, white matter microstructure (diffusion tensor imaging (DTI) measures: fractional anisotropy, mean diffusivity) before the intervention and at 7-months after training period (correlations in anodal group)

- functional neural correlates; assessed by resting-state fMRI analyses to obtain functional connectivities (seed-based connectivity: correlation of BOLD-timeseries between a seed/ROI and every voxel/location in the brain) before the intervention and at 7-months after training period (correlations in anodal group)

Inclusion Criteria: Older adults (60 - 80 years); Right handedness; subjective cognitive decline (SCD) or mild cognitive impairment (MCI) Exclusion Criteria: Dementia or other neurodegenerative neurological disorders; epilepsy or history of seizures; close relatives with epilepsy or history of seizures; previous stroke; Severe and untreated medical conditions that precludes participation in the training, as determined by responsible physician; History of severe alcoholism or use of drugs; Severe psychiatric disorders such as depression (if not in remission) or psychosis

Thams F, Kuzmina A, Backhaus M, Li SC, Grittner U, Antonenko D, Floel A. Cognitive training and brain stimulation in prodromal Alzheimer's disease (AD-Stim)-study protocol for a double-blind randomized controlled phase IIb (monocenter) trial. Alzheimers Res Ther. 2020 Nov 7;12(1):142. doi: 10.1186/s13195-020-00692-5.